Alexandra Diller Costello, a biology graduate student in the D Cornelison lab in Bond Life Sciences Center, recently received a three-year NIH fellowship from the National Heart, Blood and Lung Institute.
It provides Diller Costello with funding to pursue her work on muscle and blood vessel regeneration for three years.
The fellowship comes as a result of her proposal titled, “Signaling in the Microvasculature During Skeletal Muscle Regeneration.” Diller Costello’s research focuses on the coordination between muscles and blood vessels during muscle regeneration in adult mice. Diller Costello is also developing a novel method of 3D co-culture using primary muscle and endothelial cells to expand her investigation.
The study is part of a collaboration between the Cornelison lab at the Bond LSC and the Segal lab in the Medical Pharmacology and Physiology department at the MU School of Medicine.
Being involved in research changes perspective in and out of the lab.
Senior Rebecca Craigg came to college thinking science always had an answer.
“When I came in as a freshman I thought everything should work,” Craigg said. “If you do an experiment you should get a result. Now, I am not afraid to fail.”
Craigg joined the Cornelison lab freshman year. As a first-generation college student Rebecca was unsure of what was in store for her. But as she grew as a researcher, she also did as a person and started to understand the value of working in a lab.
“I would say my freshman year, it was a lot of ‘watch and learn,’” Craigg said. “When you figure it out, you are confident, get comfortable with it and try it on your own. This by far has helped me developed most as a person. You run into problems every day and you have to solve them, from big to small. Even though there are people to guide you, you have to run it on your own and figure it out yourself.”
The Cornelison lab researches regeneration and disease in muscles. They study how cells respond to different cell signals in order to rapidly, efficiently, and repeatedly respond to muscle damage or disease. Since freshman year Craigg has studied a specific receptor EphA7, which responds to different factors and is connected to how muscles rebuild.
This summer marks the first time Craigg has been in the lab full time, an opportunity she received by being chosen as a Cherng Summer Scholar.
“I originally started working on that project with a grad student who graduated,” Craigg said. “Now it’s become more independent and helped me develop valuable skills.”
Craigg has put those skills to work on service trips to Honduras and Nicaragua where she helped provide medical and public helth assistance and assisted with water engineering, respectively. These trips shaped her perspective on the importance of science and its lasting impacts.
“That initial exposure in the clinic where I helped give medicine to people with water borne illnesses and parasites, I felt bad, yes, but it made me think about what happens the next time,” Craigg said. “You can keep treating diseases but you need to solve the problem.”
And that’s why Craigg’s dream is to be involved with Doctors Without Borders. She wishes to create a lasting impact on the community she serves.
Craigg volunteer work also has an impact closer to home. Sophomore year Craigg started a service organization called University of Missouri Student Organization for Human and Animal Interaction, the organization volunteers at animal shelters through the Research Center for Human Animal Interaction. The club helps with research.
“Animal interaction is important for humans,” Craigg said. “They look at the importance of animals to human health and the benefits of the human animal bond.”
“#IAmScience because I feel most alive when I’m talking to people, both in and out of my field, about my work.”
While other kids were playing with Legos and dolls, Ronnie LaCombe was exploring the world through a microscope.
Alongside her cousins, LaCombe used science at an early age as both a way of learning and for entertainment.
“I’ve always wanted to be a scientist,” LaCombe said. “In third grade I told everyone I was going to be planetologist — a scientist who studies planets. Although that didn’t pan out, I guess I always knew science was the path for me.”
Years later she’s working in D Cornelison’s lab studying protein interactions in cells of rhabdomyoscarcoma, a form of childhood cancer. Specifically, the fifth-year biological sciences Ph.D. candidate is trying to uncover why a protein that’s typically on the outside of a cell is located inside the nucleus in this form of cancer.
“I was looking at the cells and saw that this protein was in the nucleus and not on the outside,” LaCombe said. “At first, I thought it was fake. I followed up on it, and it ended up being something potentially significant.”
After noticing the unusual location of the protein in the cell, LaCombe and others in her lab looked into other species to see if it existed in them, too. When they saw the structure was the same in both dogs and mice they knew it meant something.
“We were jumping up and down once as we saw it was in three different species,” LaCombe said. “That validated what we had thought earlier about it being something significant and not a mistake.”
Now, the lab’s test is to figure out why the protein is there and if it’s functioning the in the same way it would if it were outside of the cell.
“Cells touch each other and talk to each other through the proteins on the outside of the cell,” LaCombe said. “We’re trying to figure out what the protein is doing since it’s in the nucleus rather than at the surface.”
At this point, they’re still looking into how this is possible and what it means for this type of cancer.
“The hope is to figure out a method that can be used in other forms of cancer,” LaCombe said.
Until that solution is discovered, LaCombe is happy to put the puzzle together piece-by-piece.
“Research is like one very long, often very difficult, puzzle that you don’t always have all the pieces to,” LaCombe said. “I enjoy the challenge, though, and the difficulty of it makes solving the puzzle even more satisfying.”
Undergrad’s passion spurred by mice muscle regeneration research
By: Samantha Kummerer | Bond LSC
Uncertainty and curiosity led Rebecca Craigg to work in a lab.
As a first-generation college student with an interest in science but no idea what undergraduate research entailed, her path at the University of Missouri landed her in the Bond Life Sciences Center and the lab of D Cornelison.
“I honestly thought undergraduate research meant you just followed around someone like job shadowing,” she said laughing.
Now, after almost a year of research, the junior biology major is more than familiar with what working in a lab entails.
Craigg started working in Cornelison’s lab as an effort to figure out what kind of science she might be interested in. It was while she waited for her genetically altered mice to grow up when she found something that really sparked her interest.
Rather than spend her time cleaning lab dishes, Craigg began assisting a graduate student on a project studying the role of EphA7 in mice. EphA7 is a receptor on cells that helps mediate important events within the body. Receptors create a change in the body after receiving a signal from outside the cell. The exact hows and whys behind the EphA7 are still relatively unknown.
To unravel EphA7 the team began by breeding genetically altered mice with the gene switched off. Next, specific muscles were isolated, dissected, and preserved once the mice reached different developmental time points. Researchers thinly sliced the muscle and added immunofluorescent staining to track specific elements over a period of time. They marked EphA7 with a green fluorescent and regenerating muscle fibers with red. Imaging revealed every time green came up so did red. This led researchers to understand that EphA7 is connected to how muscles rebuild.
But this isn’t the only role the receptor plays.
Work this summer also discovered the gene is involved in the development of muscles. The team found at the end of development, the mice without EphA7 did not fully recover like they would have if they were not modified. When the team looked at marking for muscle stem cells, both the mice with the receptor and the mice without it had a depleted number of satellite cells, essentially muscle stem cells, that did not recover.
Craigg explained this discovery was puzzling.
In every other case heterozygous mice, the mice with one gene coded with EphA7, were fine. The team predicts the cells and muscles realized they were not adequate so the muscle stem cells began to become muscles. This process would leave fewer stem cells at the end of development.
Fewer muscle fibers really mean the mice are lacking normal muscle strength. Craigg said one reason for this could be EphA7’s relation to motor neuron axons. Motor neurons send signals from the nervous system to muscles to tell them to move. EphA7 is present on all motor neurons. The team hypothesized that the gene may play a role in guiding the motor axon to the muscle, thus without it, muscle size would decrease.
“We kind of know way more than we did, obviously, in that it’s involved in regeneration and all these things and that if a mouse doesn’t have it they have all these decreased numbers all over the board, but we don’t know why per say,” Craigg said.
To better understand why EphA7 functions the way it does, the team will begin to examine the relationship between motor neurons and EphA7. They will also explore if the type of muscle fiber, slow-twitch versus fast twitch, make a difference.
Craigg said each new piece of knowledge about EphA7 is a step towards better understanding what causes muscle disease in humans.
While the lab faces a lot more work ahead, it doesn’t faze Craigg. For her, the possibility of more discoveries is part of the thrill.
“We kept finding out so many new things about it. I would be counting things and I’d be like, ‘Oh my god, I can’t wait to get this data back, like, I just want to know,’” she exclaimed.
Rebecca Craigg is a junior biology major working in the lab of D Cornelison at Bond LSC.
Sometimes the most learning occurs outside of the classroom.
For Jacqueline Ihnat, an opportunity to pursue research at the Bond Life Sciences Center this summer will give her that chance. She recently became one of 12 Cherng Summer Scholars, a full-time, ten-week program within the Honors College at MU.
“Doing research helps keep me focused on the bigger picture,” Ihnat said. “Sometimes in class we learn things that don’t seem entirely relevant or useful, but being part of a research lab allows me to apply some of the knowledge that I gain in the classroom. It’s a daily reminder of why I’m learning what I am.”
Jacqueline Ihnat’s passion for science started in high school. Her high school biology teacher ignited that love by teaching her how to struggle through difficult problems and concepts. Now, Ihnat is an MU pre-med student with a major in business management and a minor in Spanish.
Since Ihnat is fascinated with cells and how our bodies function, she’ll be studying the role of specialized stem cells in muscle regeneration and how they interact with muscle fibers — specifically the role of Eph-A3, a type of cell-surface receptor. This project will take place in the lab of Dawn Cornelison, a Bond LSC biologist who will be mentoring Ihnat this summer.
Each muscle in the body is unique in its length, fiber organization and fiber type patterning, so Ihnat hopes to explore why two types of muscle — fast and slow twitch muscle — develop and regenerate to maintain each specific muscle fiber-type composition.
When a muscle is damaged from exercise or injury, a muscle’s stem cells, or “satellite cells,” will multiply, move towards the injury and form new muscle, replacing the damaged fiber. There is no research that determines if “fast” satellite cells create fast fibers and if “slow” satellite cells create slow fibers, and Ihnat hopes to tackle that question this summer. This kind of research gives scientists a deeper understanding of degenerative muscle diseases such as ALS, which could lead to more effective treatments and therapies.
The Cherng Summer Scholars program is supported by a gift from Andrew and Peggy Cherng and the Panda Charitable Foundation. The Cherng’s are the founders of Panda Express, a well-known restaurant chain. These scholarships support individually designed theoretical research, applied research or artistry projects under the mentorship of an MU faculty member.
For young scientists who are just starting to conduct research and struggling to feel successful, Ihnat has a few words of motivation.
“My high school biology teacher always said that research is 30 years of frustration and disappointment followed by 30 seconds of elation when you finally make a breakthrough,” she said. “Patience is key.”